Each year in the United States, there are an estimated 4 million cases of pneumonia, accounting for 600,000 hospitalizations with an annual cost of $23 billion. Alcohol is a common risk factor for the development of both community-acquired and nosocomial pneumonia. Presently, the mechanisms by which chronic alcohol abuse alters human pulmonary immunity and increases the likelihood of developing pneumonia are essentially unknown. We hypothesize that increased oxidative stress via glutathione (GSH) depletion leads to abnormal function and viability of human alveolar macrophages (AM), and subsequently impairs alveolar clearance of infectious particles leading to pulmonary infections. In this proposal, the impact of alcohol abuse on the development of pneumonia will be explored by examining the function and viability of AM obtained from two patient cohorts: individuals with a prior history of chronic alcohol abuse and critically ill patients with acute lung injury. Additionally, we will determine the efficacy of oral antioxidant replacement therapy on AM function in individuals with a prior history of chronic alcohol abuse. The goal of this research endeavor is effective medical therapy to decrease the risk of community-acquired and nosocomial pneumonia in the millions of individuals who chronically abuse alcohol. Dr. Ellen Burnham is presently a fellow in Pulmonary and Critical Care Medicine at Emory University. During the next five years, she will work with several investigators in the Emory Alcohol and Critical Care Clinical Research Program in order to develop necessary clinical and basic research skills. With the support of this proposal, Dr. Burnham will not only receive personal supervision from these established clinical and basic investigators, but will also enroll in the Clinical Research Curriculum Award (CRCA) program at Emory University and the Rollins School of Public Health, and obtain a Masters of Science in Clinical Research to further enhance her ability to perform high-quality research. The ultimate goal of this award is to develop an independent research career in "translational" investigation for Dr. Burnham, examining the systemic effects of alcohol abuse as it relates to pulmonary and critical care medicine.